title: Thermal stability of apolipoprotein B100 in low-density lipoprotein is disrupted at early stages of oxidation while neutral lipid core organization is conserved.
abstract: The time course of the unfolding characteristics of the protein moiety and of the thermotropic behavior of the core-located apolar lipids of highly homogeneous low-density lipoprotein (LDL) subspecies (d 1.030-1.040 g/mL) have been evaluated during transition metal- and azo radical-induced oxidation using differential scanning calorimetry. Apolipoprotein B100 (apo-B100) structure was highly sensitive to oxidative modification; indeed, a significant loss of thermal stability was observed at initial stages irrespective of whether oxidation was mediated by site-specific binding of copper ions or by free radicals generated during decomposition of azo compounds. Subsequently, thermal protein integrity was destroyed, as a result of potentially irreversible protein unfolding, cross-linking reactions, and aggregation. Our results suggest that even minimal oxidative modification of apo-B100 has a major impact on the stability of this large monomeric protein. By contrast, the core lipids, which consist primarily of cholesteryl esters and triglycerides and play a determinant role in the thermal transition occurring near physiological temperature, preserved features of an ordered arrangement even during propagation of lipid peroxidation.
authors.affiliation: Institute of Biophysics, Austrian Academy of Sciences, Graz.
authors.forename: R
authors.initials: R
authors.lastname: Prassl
authors.forename: B
authors.initials: B
authors.lastname: Schuster
authors.forename: P
authors.initials: P
authors.lastname: Laggner
authors.forename: C
authors.initials: C
authors.lastname: Flamant
authors.forename: F
authors.initials: F
authors.lastname: Nigon
authors.forename: M J
authors.initials: MJ
authors.lastname: Chapman
mesh_terms: D000578:Amidines / Q000494:pharmacology; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B / Q000737:chemistry / Q000378:metabolism*; D002152:Calorimetry, Differential Scanning; D003300:Copper / Q000494:pharmacology; D006358:Hot Temperature; D006801:Humans; D050356:Lipid Metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008055:Lipids / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000578:Amidines; D053299:Apolipoprotein B-100; D001055:Apolipoproteins B; D008055:Lipids; D008077:Lipoproteins, LDL; C046728:2,2'-azobis(2-amidinopropane); D003300:Copper